MASH - Metabolic Dysfunction-Associated Steatohepatitis, NASH - Nonalcoholic Steatohepatitis
Conditions
Brief summary
This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with compensated cirrhosis due to NASH/MASH.
Interventions
DRUGEfruxifermin
Administered by subcutaneous injection
DRUGPlacebo
Administered by subcutaneous injection
Sponsors
Akero Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Cohort 1: Biopsy proven compensated cirrhosis (fibrosis stage 4) due to NASH/MASH and NAS score of \>=3 (at least 1 in each category) or evidence of steatosis and 2 current features of metabolic comorbidities * Cohort 2: Biopsy proven or non-invasively diagnosed compensated cirrhosis (fibrosis stage 4) due to NASH/MASH
Exclusion criteria
* Other causes of liver disease based on medical history and/or liver histology and/or central laboratory results * Type 1 diabetes or unstable Type 2 diabetes * Any current or prior history of decompensated liver disease Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1 only: Proportion of subjects with ≥ 1 stage improvement in fibrosis and no worsening of steatohepatitis | 96 Weeks | Based on NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis) |
| Time from randomization to the first significant clinical event including disease progression, liver decompensation events, etc. | 5 years | Measured by composite of protocol-specified clinical events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of non-invasive markers of liver fibrosis | 96 Weeks, 5 Years | ELF (scale of 6.7 to 11.3 with higher scores indicative of increased fibrosis) |
| Change from baseline of markers of liver injury | 96 Weeks, 5 Years | ALT (U/L) and AST (U/L) |
| Change from baseline of lipoproteins | 96 Weeks, 5 Years | Total cholesterol (mg/dL), Triglycerides (mg/dL), HDL-C (mg/dL), Non-HDL-C (mg/dL), and LDL-C (mg/dL) |
| Change from baseline of markers of insulin sensitivity and glycemic control | 96 Weeks, 5 Years | HbA1c (%) |
| Change from baseline of body weight (kg) | 96 Weeks, 5 Years | — |
| Safety and tolerability of EFX through the reporting of extent of exposure (weeks) | From first dose through end of study (up to 5 Years) | — |
| Safety and tolerability of EFX through the reporting of adverse events (frequency of events) | From first dose through end of study (up to 5 Years) | Proportion of subjects reporting adverse events |
| Safety and tolerability of EFX through the reporting of adverse events (severity of events) | From first dose through end of study (up to 5 Years) | Proportion of subjects reporting adverse events |
| Number of participants with abnormal laboratory tests results, abnormal ECGs, abnormal ultrasounds, abnormal vital sign assessments | From first dose through end of study (up to 5 years) | — |
| Cohort 1 only: Proportion of subjects with ≥ 1 stage improvement in fibrosis and no worsening of steatohepatitis | 5 Years | Based on NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis) |
| Cohort 1 only: Proportion of subjects with ≥ 1 stage improvement in fibrosis | 96 Weeks | Based on NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis) |
| Cohort 1 only: Proportion of subjects with Resolution of NASH/MASH and a ≥ 1 stage improvement in fibrosis | 96 Weeks | Based on NAS (scored by 0-1 for steatosis, 0-3 for inflammation, and 0-2 for ballooning) and NASH CRN fibrosis score (scored by a fibrosis score of 0-4, where 0 = no fibrosis, 1 = centrilobular pericellular fibrosis, 2 = centrilobular and periportal fibrosis, 3 = bridging fibrosis, 4 = cirrhosis) |
| Cohort 1 only: Proportion of subjects with Resolution of NASH/MASH | 96 Weeks | Based on NAS (scored by 0-1 for steatosis, 0-3 for inflammation, and 0-2 for ballooning) |
Countries
Argentina, Australia, Brazil, Canada, Chile, France, Germany, India, Israel, Italy, Japan, Mexico, Poland, Puerto Rico, South Korea, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAkero Study Director
Outcome results
None listed